G.O.13: One year follow-up of Duchenne muscle dystrophy with nuclear magnetic resonance imaging and spectroscopy indices

Abstract

The evolution of quantitative NMR imaging (NMRI) and spectroscopy (NMRS) indices over one year is reported in forearms of 21 Duchenne Muscular Dystrophy (DMD) patients amenable to exon 53 skipping therapy. Patients aged 6 to 18 yrs, 12 non-ambulant at inclusion, were followed up to characterize course of natural disease in upper limbs, which are to be targeted in future trials. Boys underwent NMR at 3T, with arm resting along the body. The two arms were examined in separate sessions on the same day, and repeated at a one year interval. Examinations comprised NMRI (measurement of T2 of muscle water and of fat fraction by 3-point Dixon imaging) in flexor and extensor muscles (FLEX, EXT) and non localized NMRS of phosphate metabolites. Each item lasted ∼20 min. Compared to data obtained in arms of 7 control subjects (aged 7–20), the data at inclusion in patients showed muscle water T2, deconvoluted from fat, was above 95% confidence limits in 20% of cases, with excessive T2 heterogeneity in 33%. Percentage fat signal (%F) exceeded 6.6%in 80% of cases and FLEX had higher %F than EXT muscles. Metabolic ratios combining ATP, phosphocreatine, phospho mono- and di-esters and two pools of inorganic phosphate: cytosolic (Pia) and an anomalous alkaline pool present in dystrophic muscle (Pib) were abnormal in 80–100% of cases and correlated strongly to %F. These indices progressed markedly faster after loss of ambulation. After one year, %F increased by 1.0% on average ( p p = 0.02); Pib/Ptot (+10%, p = 0.04), Pia/Pitot (−5%, p = 0.04), were always highest and most significant in non-ambulant patients. NMRI and NMRS markers quantified disease progression in metabolism and fat infiltration in arms of DMD boys over one year. Progression appeared most marked for those muscles that were already severely affected.